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Assessing the antibacterial potential of 6-gingerol: Combined experimental and computational approaches
Saudi Pharmaceutical Journal ( IF 4.1 ) Pub Date : 2024-03-18 , DOI: 10.1016/j.jsps.2024.102041
Mahmoud A. Elfaky , Hassan M. Okairy , Hossam M. Abdallah , Abdulrahman E. Koshak , Gamal A. Mohamed , Sabrin R.M. Ibrahim , Abdulrahim A. Alzain , Wael A.H. Hegazy , El-Sayed Khafagy , Noura M. Seleem

The rise of antibiotic resistance in bacteria is becoming a global concern, particularly due to the dwindling supply of new antibiotics. This situation mandates the discovery of new antimicrobial candidates. Plant-derived natural compounds have historically played a crucial role in the development of antibiotics, serving as a rich source of substances possessing antimicrobial properties. Numerous studies have supported the reputation of 6-gingerol, a prominent compound found in the ginger family, for its antibacterial properties. In this study, the antibacterial activities of 6-gingerol were evaluated against Gram-negative bacteria, and , with a particular focus on the clinically significant Gram-negative and Gram-positive bacteria . Furthermore, the anti-virulence activities were assessed , , and . The current findings showed that 6-gingerol’s antibacterial activity is due to its significant effect on the disruption of the bacterial cell membrane and efflux pumps, as it significantly decreased the efflux and disrupted the cell membrane of and . Furthermore, 6-gingerol significantly decreased the biofilm formation and production of virulence factors in and in concentrations below MICs. The anti-virulence properties of 6-gingerol could be attributed to its capacity to disrupt bacterial virulence-regulating systems; quorum sensing (QS). 6-Gingerol was found to interact with QS receptors and downregulate the genes responsible for QS. In addition, molecular docking, and molecular dynamics (MD) simulation results indicated that 6-gingerol showed a comparable binding affinity to the co-crystalized ligands of different QS targets as well as stable interactions during 100 ns MD simulations. These findings suggest that 6-gingerol holds promise as an anti-virulence agent that can be combined with antibiotics for the treatment of severe infections.

中文翻译:

评估 6-姜酚的抗菌潜力:实验和计算相结合的方法

细菌抗生素耐药性的上升正在成为全球关注的问题,特别是由于新抗生素供应的减少。这种情况要求发现新的候选抗菌药物。植物源性天然化合物历来在抗生素的开发中发挥着至关重要的作用,是具有抗菌特性的物质的丰富来源。许多研究都支持 6-姜酚(姜科中发现的一种重要化合物)的抗菌特性。在这项研究中,评估了 6-姜酚对革兰氏阴性菌的抗菌活性,特别关注临床上显着的革兰氏阴性菌和革兰氏阳性菌。此外,还评估了抗毒力活性。目前的研究结果表明,6-姜酚的抗菌活性是由于其对细菌细胞膜和外排泵的破坏有显着影响,因为它显着减少了外排并破坏了 和 的细胞膜。此外,6-姜酚在低于 MIC 的浓度下显着降低生物膜的形成和毒力因子的产生。 6-姜酚的抗毒力特性可归因于其破坏细菌毒力调节系统的能力;群体感应(QS)。 6-姜酚被发现与 QS 受体相互作用并下调负责 QS 的基因。此外,分子对接和分子动力学(MD)模拟结果表明,6-姜酚与不同QS靶标的共晶配体具有相当的结合亲和力,并且在100 ns MD模拟期间显示出稳定的相互作用。这些发现表明,6-姜酚有望作为一种抗毒剂,可与抗生素联合治疗严重感染。
更新日期:2024-03-18
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